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    PRODUCTION OF HOMOTRIMERIC FUSION PROTEINS
    1.
    发明申请
    PRODUCTION OF HOMOTRIMERIC FUSION PROTEINS 审中-公开
    共培养融合蛋白的生产

    公开(公告)号：US20090192291A1

    公开(公告)日：2009-07-30

    申请号：US12353713

    申请日：2009-01-14

    申请人： James W. West ,  Cameron S. Brandt ,  Stephen R. Jaspers

    发明人： James W. West ,  Cameron S. Brandt ,  Stephen R. Jaspers

    IPC分类号： C07K14/00

    CPC分类号： C07K14/47 ,  C07K14/705 ,  C07K14/70575 ,  C07K14/70578 ,  C07K14/78 ,  C07K2319/00 ,  C07K2319/03 ,  C12N15/62

    摘要： The present invention provides method for producing trimeric tumor necrosis factor receptors that are potent inhibitors of their cognate ligands. More particularly, the present invention provides polypeptides that comprise: (1) an extracellular domain of the transmembrane activator and CAML (calcium-signal modulating cyclophilin ligand) interactor (TACI), and (2) a trimerizing polypeptide. Suitable TACI extracellular domains include: (1) amino acid residues 30 to 110 of SEQ ID NO:4, (2) amino acid residues 1 to 110 of SEQ ID NO:4, (3) amino acid residues 30 to 154 of SEQ ID NO:4, and (4) amino acid residues 1 to 154 of SEQ ID NO:4. Illustrative trimerizing polypeptides include a trimerizing fragment of Heat Shock Binding Protein-1. The present invention further provides homotrimeric complexes of fusion proteins comprising a TACI extracellular domain and a trimerizing polypeptide.

    摘要翻译： 本发明提供了产生三聚体肿瘤坏死因子受体的方法，所述三聚体肿瘤坏死因子受体是其相关配体的有效抑制剂。 更具体地，本发明提供多肽，其包含：（1）跨膜激活剂的胞外结构域和CAML（钙信号调节亲环蛋白配体）相互作用体（TACI），和（2）三聚体多肽。 合适的TACI细胞外结构域包括：（1）SEQ ID NO：4的氨基酸残基30至110，（2）SEQ ID NO：4的氨基酸残基1至110，（3）SEQ ID NO：4的氨基酸残基30至154 NO.4和（4）SEQ ID NO：4的氨基酸残基1至154。 示例性的三聚化多肽包括热休克结合蛋白-1的三聚体片段。 本发明还提供了包含TACI胞外域和三聚多肽的融合蛋白的同源三聚体。

    Protease activatable interferon alpha proprotein
    4.
    发明授权
    Protease activatable interferon alpha proprotein 有权
    蛋白酶活化的干扰素α前蛋白

    公开(公告)号：US08399219B2

    公开(公告)日：2013-03-19

    申请号：US12711199

    申请日：2010-02-23

    申请人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Jason Sagert

    发明人： Nancy E. Stagliano ,  James W. West ,  Kathryn Kamath ,  Paul H. Bessette ,  Jason Sagert

    IPC分类号： C12P21/04 ,  C12N5/10 ,  C12N15/00 ,  A61K38/21 ,  C07H21/04

    CPC分类号： C07K14/56 ,  A61K38/00 ,  A61K47/64 ,  A61K47/65 ,  C07K14/00 ,  C07K14/555 ,  C07K14/565 ,  C07K14/57 ,  C07K14/705 ,  C07K16/00 ,  C07K19/00 ,  C07K2319/10 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/50 ,  C07K2319/70 ,  C07K2319/90 ,  C12N15/1037 ,  G01N33/6866

    摘要： The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.

    摘要翻译： 本公开内容提供了蛋白质和可激活的前蛋白组合物。 前蛋白含有功能蛋白（即其全长蛋白质或其功能片段），其与抑制功能蛋白与其靶标或结合配偶体的结合的肽掩模偶联。 可激活的蛋白质包含与肽掩模偶联的功能性蛋白质，并进一步与可活化接头偶联，其中在非活化状态下，肽掩模抑制功能性蛋白质与其靶标或结合配偶体的结合，并且在活化状态下 肽掩模不抑制功能蛋白与其靶或结合配偶体的结合。 前体蛋白可以提供如果不抑制结合其结合配偶体的功能性蛋白质在非处理部位的结合，则可以提供降低的毒性和不良副作用。 前体蛋白可进一步提供改善的生物分布特征。 含有肽掩模的前体蛋白可以显示比不含肽掩模的相应功能蛋白质更长的体内或血清半衰期。 本公开进一步提供筛选，制备和使用这些蛋白质的方法。

    Methods for targeting cells that express fibroblast growth receptor-3 or -2
    7.
    发明授权
    Methods for targeting cells that express fibroblast growth receptor-3 or -2 有权
    靶向表达成纤维细胞生长受体-3或-2的细胞的方法

    公开(公告)号：US07470665B2

    公开(公告)日：2008-12-30

    申请号：US10354859

    申请日：2003-01-29

    申请人： James W. West

    发明人： James W. West

    IPC分类号： A61K38/18 ,  C07K14/50 ,  C07K14/415 ,  C07K19/00

    CPC分类号： C07K16/46

    摘要： Fibroblast growth factor-18 (FGF-18) binds with FGF receptors-2 and -3. Compositions comprising an FGF-18 component can be used to target cells that express these receptors. Suitable targets include tumor cells that express constitutively activated forms of FGF receptors-2 and -3. For example, conjugates of FGF-18 and saporin can be used to target tumor cells that express FGF receptors-2 or -3, and to inhibit the proliferation of these cells.

    摘要翻译： 成纤维细胞生长因子-18（FGF-18）与FGF受体-2和-3结合。 包含FGF-18组分的组合物可用于靶向表达这些受体的细胞。 合适的靶标包括表达组成型活化形式的FGF受体-2和-3的肿瘤细胞。 例如，FGF-18和saporin的缀合物可用于靶向表达FGF受体-2或-3的肿瘤细胞，并抑制这些细胞的增殖。

    Heterodimeric four helix bundle cytokines
    8.
    发明授权
    Heterodimeric four helix bundle cytokines 有权
    异二聚体四螺旋束细胞因子

    公开(公告)号：US07445772B2

    公开(公告)日：2008-11-04

    申请号：US11675890

    申请日：2007-02-16

    申请人： James W. West ,  Stacey Tannheimer

    发明人： James W. West ,  Stacey Tannheimer

    IPC分类号： A61K38/19

    CPC分类号： C07K14/5434 ,  A61K38/00 ,  C12N15/62 ,  Y10S514/885

    摘要： Heterodimeric proteins comprising two helical bundle cytokines are disclosed. One of the polypeptides comprises zsig81 and a second polypeptide which comprises either p19 (aka IL-12A) or p35 (aka IL-12A). The proteins may be produced as fusion proteins or expressed as a single chain. The heterdimeric protein comprising zsig81 and p19 is designated zcyto33f2 and the heterodimeric protein comprising zsig81 and p35 is designated zcyto35f2. Zcyto33f2 and zcyto35f2 proteins are associated with epithelial cell types, including lung and gut epithelium, and may play a role in physiological conditions such as inflammation.

    摘要翻译： 公开了包含两个螺旋束细胞因子的异二聚体蛋白。 多肽中的一种包含zsig81和包含p19（又名IL-12A）或p35（又名IL-12A）的第二多肽。 蛋白质可以作为融合蛋白产生或表达为单链。 包含zsig81和p19的杂二聚体蛋白质被命名为zcyto33f2，包含zsig81和p35的异二聚体蛋白质被命名为zcyto35f2。 Zcyto33f2和zcyto35f2蛋白与上皮细胞类型（包括肺和肠上皮）相关，并且可能在诸如炎症的生理条件中起作用。

    Optical flameout detector
    9.
    发明授权
    Optical flameout detector 失效
    光学熄火检测器

    公开(公告)号：US5748090A

    公开(公告)日：1998-05-05

    申请号：US892833

    申请日：1997-07-16

    申请人： Stephen E. Borg ,  James W. West ,  Robert M. Lawrence ,  Samuel E. Harper, Jr. ,  David W. Alderfer

    发明人： Stephen E. Borg ,  James W. West ,  Robert M. Lawrence ,  Samuel E. Harper, Jr. ,  David W. Alderfer

    IPC分类号： F23N5/08 ,  G08B17/12

    CPC分类号： F23N5/082 ,  F23N2029/14

    摘要： A device has been developed which monitors the presence of a flame within a combustion chamber. The optical flameout detection system responds to gross changes in combustor light intensity, which is monitored in two spectral bands. A photomultiplier tube makes optical measurements in the ultraviolet portion of the spectrum, and a silicon photodiode covers the visible region. The detectors, located outside the combustion chamber, receive the light energy radiated from the combustion process through fiber optic probes designed to operate in a high pressure environment. The optical fibers are aimed diagonally through the center of the injector at the combustion chamber wall downstream of the injector. The probed observe events occurring within a narrow conical-shaped field of view so that the system can quickly detect longitudinal movement of the flame front away from the injector. If a change in intensity of the flame is detected, the fuel supply to the combustion chamber is shut off, limiting the amount of unburned fuel in the combustion chamber which could reignite.

    摘要翻译： 已经开发了一种监测燃烧室内火焰存在的装置。 光学熄火检测系统响应于在两个光谱带中监测的燃烧器光强度的总变化。 光电倍增管在光谱的紫外部分进行光学测量，硅光电二极管覆盖可见光区域。 位于燃烧室外的探测器通过被设计成在高压环境中工作的光纤探头接收从燃烧过程辐射的光能。 在注射器下游的燃烧室壁处，光纤被对角地穿过喷射器的中心。 探测到的观察事件发生在窄锥形视野内，使得系统可以快速检测火焰前端远离喷射器的纵向运动。 如果检测到火焰的强度变化，则关闭燃烧室的燃料供给，从而限制燃烧室中可能重燃的未燃烧燃料的量。